In this proposal for a Mentored Research Scientist Development Award (K01), Amanda Hyre Anderson, PhD, MPH, outlines her career goals, career development plan, environment, mentoring framework, and research project to examine modifiable and biochemical predictors and consequences of acute kidney injury (AKI) in chronic kidney disease (CKD). Dr. Anderson completed her master's and doctoral training in Epidemiology at Tulane University with numerous awards and honors, and finished a NRSA postdoctoral fellowship in Renal Epidemiology at the University of Pennsylvania School of Medicine. She is currently a Research Associate at Penn and a co-investigator on the Chronic Renal Insufficiency Cohort (CRIC) Study. Dr. Anderson plans to pursue a career as an independent investigator to study the epidemiology of AKI in CKD, characterization and prediction of kidney function decline over time, and insufficiently examined co-morbidities and outcomes (e.g., non-cardiovascular co-morbidities) associated with CKD. Her long-term goal is to hold a standing faculty position as an active investigator. To enable her transition from mentored scientist to independent investigator during the award period, Dr. Anderson will 1) seek an improved knowledge of renal disease through coursework and nephrology rounds, 2) pursue an expanded repertoire of sophisticated statistical methods through coursework and mentoring, 3) strengthen her leadership capabilities by completing a leadership development program through the Wharton School of Business and engaging in CRIC Study oversight activities, 4) leverage interactions with mentors and consultants to refine her research plan and support her career development, and 5) submit an R01 application to further her independent research program. The overall goal of the proposed K01 research project is to identify modifiable and biochemical risk factors for AKI, and to examine the impact of AKI on morbidity and mortality among a diverse group of extremely well- characterized CRIC participants with CKD. More specifically, the aims of the project are: 1) to examine poor glycemic control, inadequate control of blood pressure, elevated body mass index, and use of renin- angiotensin-system blockade, diuretics, and nonsteroidal anti-inflammatory drugs as modifiable risk factors for AKI in the setting of CKD, 2) to investigate inflammatory and kidney injury markers, as well as CKD severity, as risk factors for AKI in CKD, and 3) to examine the impact of AKI on subsequent mortality and morbidity in CKD. All proposed investigations will occur within the cohort framework of the CRIC Study utilizing Cox proportional hazards models, mixed effects growth curve models, and marginal structural models with time-updated exposures. An innovative mixed effects approach will be employed among CRIC participants who experience AKI during follow-up to compare the slope of kidney function decline before and after the AKI episode. This study will make possible the identification of potentially modifiable, and thus, clinically-actionable, risk factors for AKI, and improve our understanding of the impact of AKI on the course of CKD. PUBLIC HEALTH RELEVANCE: The proposed research project aims to identify modifiable and biochemical risk factors for acute kidney injury (AKI), and to examine the impact of AKI on morbidity and mortality among a diverse group of extremely well- characterized individuals with chronic kidney disease (CKD). This study will make possible the identification of potential interventions to reduce the risk of AKI in CKD, and improve our understanding of the impact of AKI on the course of CKD.